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Original Investigation |

Maintenance Treatment Is Not Necessary After Helicobacter pylori Eradication and Healing of Bleeding Peptic Ulcer:  A 5-Year Prospective, Randomized, Controlled Study FREE

Chen-Chiung Liu, MD; Chia-Long Lee, MD; Chung-Chuan Chan, MD; Tien-Chien Tu, MD; Chien-Chung Liao, MD; Chi-Hwa Wu, MD; Tzen-Kwan Chen, MD
[+] Author Affiliations

From the Division of Gastroenterology, Department of Internal Medicine, Cathay General Hospital (Drs Liu, Lee, Chan, Tu, Liao, Wu, and Chen), and the School of Medicine, Taipei Medical University (Dr Lee), Taipei, Taiwan. The authors have no relevant financial interest in this article.


Arch Intern Med. 2003;163(17):2020-2024. doi:10.1001/archinte.163.17.2020.
Text Size: A A A
Published online

Background  It is well accepted that in patients with uncomplicated peptic ulcers, Helicobacter pylori eradication therapy does not need to be followed by further antisecretory treatment. However, it is uncertain whether patients with bleeding peptic ulcers should receive maintenance antiulcer therapy after successful H pylori eradication and ulcer healing. The aim of this 5-year, prospective, randomized, controlled study was to investigate the role of long-term maintenance therapy after successful H pylori eradication and healing of bleeding ulcers.

Methods  A total of 82 consecutive patients with H pylori–associated bleeding peptic ulcers were enrolled in the study. After successful H pylori eradication with the 1-week proton pump inhibitor–based triple therapy and an additional 3-week treatment with 20 mg of omeprazole daily for ulcer healing, the patients were assigned to one of four 16-week maintenance treatment groups as follows: group A received 15 mL of an antacid suspension 4 times daily; group B received 300 mg of colloidal bismuth subcitrate 4 times daily; group C received 20 mg of famotidine twice daily; and group D, the control group, received placebo twice daily. Follow-up included an urea breath test labeled with carbon 13, biopsy-based tests, and repeated endoscopic examination.

Results  An analysis of variance revealed no difference in mean age and mean follow-up time among the groups. During a mean follow-up of 56 months, there was no peptic ulcer recurrence among the 3 treatment groups, and all of the patients remained free of H pylori infection during the study period.

Conclusions  In patients with bleeding peptic ulcers, antiulcer maintenance treatment was not necessary to prevent ulcer recurrence after successful H pylori eradication and ulcer healing. In addition, the 1-week proton pump inhibitor–based triple therapy had the efficacy to ensure long-term eradication of H pylori in a region of high prevalence.

Figures in this Article

GASTROINTESTINAL hemorrhage, one of the most frequent complications of peptic ulcer disease, is associated with substantial morbidity, mortality, and health care costs.1 Despite advances in diagnosis and treatment in the past decade, the mortality rate from upper gastrointestinal hemorrhage still remains around 6% to 14% and bleeding reoccurs after initial hemostasis in about 10% to 30% of patients with bleeding peptic ulcers.14 To prevent recurrent ulcer bleeding is therefore a highly desirable clinical goal.

The importance of Helicobacter pylori in the pathogenesis of peptic ulcers and in ulcer recurrence is well established. At present, ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) and H pylori infection are recognized as the 2 major factors predisposing to bleeding peptic ulcers.1 Previous studies have shown that eradication of H pylori infection is associated with a significant decrease in the rate of ulcer recurrence.57 In a long-term study of patients with uncomplicated ulcer disease who did not use NSAIDs or maintenance antisecretory therapy, the recurrence of duodenal or gastric ulcers was completely prevented during a median follow-up of 2.5 years after successful H pylori eradication therapy.8 However, whether patients with bleeding peptic ulcers should receive the same treatment as patients with uncomplicated ulcers, with no antiulcer maintenance therapy after successful H pylori eradication and ulcer healing, is uncertain.

The main purpose of our 5-year, prospective, randomized, controlled study was to investigate the need for maintenance therapy in the long-term management of patients after successful H pylori eradication therapy and subsequent healing of a bleeding ulcer. In addition, we assessed the long-term success rate of H pylori eradication after the 1-week proton pump inhibitor (PPI)–based triple therapy in Taiwanese patients with complicated ulcers.

This study was conducted at Cathay General Hospital, Taipei, Taiwan. Patients presenting with upper gastrointestinal tract bleeding from June 1996 to March 1998 were considered for enrollment. The inclusion criteria were diagnosis of H pylori infection, plus endoscopic evidence of active peptic ulcer bleeding or any one of the following stigmata of recent ulcer hemorrhage: red or black spots in the ulcer base, blood clot adherent to the ulcer base, or visible vessel end. Peptic ulcers were identified as disruptions in the mucosa measuring no less than 5 mm in diameter, with an apparent depth.9 Patients with a history of gastric surgery or specific antiulcer treatment, or who used antibiotics or NSAID within 2 weeks prior to admission, were excluded. Informed consent was obtained from each patient before the procedures were performed.

ASSESSMENT OF H PYLORI STATUS

The diagnosis of H pylori infection was based on the results of invasive and noninvasive tests. A total of 4 biopsy specimens were taken from the gastric mucosa for each patient: 1 antral specimen for a rapid urease test (CLO test; Delta West Pty Ltd, Bently, Australia); 1 antral specimen and 1 specimen from the corpus for histologic evaluation; and 1 antral specimen for bacterial culture (ground in blood agar in a 5% microaerobic environment). Noninvasive methods included the 15-minute urea breath test labeled with 100 mg of carbon 13 (13C-UBT) (INER-HP 13U-Tester; Lungtan, Taiwan), and an enzyme-linked immunosorbent assay. The 13C-UBT was considered positive when the value gradient of the 13C/12C ratio between baseline and test gas sample was greater than 0.3%; and the enzyme-linked immunosorbent assay (AMRAD Operations Pty Ltd, Melbourne, Australia) for blood IgG antibodies was considered positive when the titer was greater than 30 U/mL. A positive diagnosis of H pylori infection required a positive culture, a positive histologic finding, or a positive result for 2 of the following tests: CLO test, 13C-UBT, and enzyme-linked immunosorbent assay.

STUDY DESIGN

Most patients were hospitalized and underwent nasogastric tube drainage of stomach contents. During hospitalization, treatment with intravenous administration of H2-blockers and oral antacid suspensions, but without PPIs, was allowed. Once patients could be discharged or eat normally, a PPI-based triple therapy was initiated. Each patient received 20 mg of omeprazole, 250 mg of clarithromycin, and 500 mg of metronidazole orally twice daily (bid) for 1 week, followed by a 3-week treatment of 20 mg of omeprazole once daily to heal the ulcer. Endoscopic examination was repeated at least 4 weeks after treatment completion for the assessment of ulcer healing. The 13C-UBT and 2 biopsy-based tests (an histologic examination and the CLO test) were performed again to determine whether the patient was free of H pylori infection. Helicobacter pylori infection was considered to be eradicated when a negative histologic finding and a negative result for either of the other tests (the CLO test and the 13C-UBT) were obtained. Otherwise, the eradication was considered unsuccessful. If H pylori had not been successfully eradicated, the patient was excluded from the study and another regimen was given. It was a quadruple therapy consisting of 150 mg of ranitidine bid, 500 mg of tinidazole bid, 250 mg of amoxicillin 4 times daily (qid), and 300 mg of colloidal bismuth subcitrate qid for 2 weeks. After confirmation of H pylori eradication, patients were divided into 4 groups by a computer-generated table of random numbers and received different maintenance treatment regimens for 16 weeks. The treatment regimens were as follows: group A received 15 mL of an antacid suspension (aluminum-magnesium-hydrate and dimethyl polysiloxane) qid; group B received 300 mg of colloidal bismuth subcitrate qid; group C received 20 mg of famotidine bid; and group D, the control group, received placebo bid.

FOLLOW-UP SCHEDULE AND STATISTICAL ANALYSIS

After receiving the 16-week maintenance treatment, all patients were asked to report to the outpatient clinics every 4 months in the first year, and then at 6-month intervals until the end of the study in 2002. The 13C-UBT was performed at 4-month intervals during the first year and at 1-year intervals thereafter for the assessment of H pylori status (Figure 1). If a 13C-UBT result was newly positive, the patient underwent a follow-up endoscopic examination followed by a CLO test to confirm the presence of H pylori infection. All patients were instructed to contact the responsible physician if ulcerlike symptoms occurred, and endoscopic evaluation was repeated for possible peptic ulcer recurrence. A 13C-UBT and a CLO test were performed to assess H pylori status during the same visit. If patients missed a follow-up visit, they were contacted by telephone. If they refused to return, they were interviewed by phone about the recurrence of gastrointestinal bleeding and ulcer symptoms.

Place holder to copy figure label and caption

Summary of the study design and flow diagram of the progress of participants. PPI indicates proton pump inhibitor; 13C-UBT, urea breath test labeled with 100 mg of carbon 13.

Graphic Jump Location

The different rates of recurrent peptic ulcer in the 4 groups were compared using an analysis of variance. A P value of less than .05 was considered statistically significant.

The study was completed in February 2002. A total of 99 patients (78 patients with bleeding duodenal ulcers, 11 patients with bleeding gastric ulcers, and 10 patients with bleeding duodenal and gastric ulcers) were recruited for participation in the study. Their characteristics are shown in the following tabulation:

A blood transfusion was required in some patients to maintain their hemodynamic status (Table 1). A follow-up endoscopic examination, performed after the 1-week PPI-based triple therapy and an additional 3 weeks of omeprazole therapy, showed that ulcer healing had occurred in all of the recruited patients (100%). However, H pylori eradication had failed in 7 patients who were thus excluded. The H pylori eradication rate for our 1-week PPI-based triple therapy was 92.9% (92/99).

Table Graphic Jump LocationTable 1. General Characteristics of 99 Patients With Bleeding Peptic Ulcers

Of the 92 patients with bleeding peptic ulcers whose H pylori infections had been eradicated and ulcers had healed, 82 agreed to receive 16 weeks of maintenance therapy and were randomized to receive 1 of 4 treatment regimens. The other 10 patients refused further management but agreed to be followed up, and were therefore designated as the contrast group. An analysis of variance revealed no statistically significant differences among the 4 treatment groups regarding mean age and mean follow-up time. One patient died of myocardial infarction during the second year and 4 patients were lost to follow-up. Their mean age was 61 years (range, 55-73 years) and their mean follow-up time was 18 months (range, 12-28 months). Therefore, only 77 patients adhered to the protocol until the end of the follow-up period (Table 2). The mean age of these 77 patients was 49 years (range, 20-76 years), and their mean follow-up time was 56 months (range, 44-66 months).

Table Graphic Jump LocationTable 2. Medications and Clinical Characteristics of Patients Who Completed the Study*

During the 56-month follow-up, 38 patients underwent endoscopic examination because of recurrent ulcerlike symptoms. No evidence of ulcer relapse or bleeding recurrence was found, however, and all of these patients remained free of H pylori infection (Table 3). One male patient in group C reported hematemesis after 45 months of follow-up. Emergency endoscopic examination revealed Mallory-Weiss syndrome but no recurrent gastric or duodenal ulcer was detected. The other patients who did not choose to undergo repeated endoscopic evaluations reported no symptoms or signs of recurrent peptic ulcer during the entire follow-up period. An analysis of variance showed no differences among the 4 groups regarding the absence of ulcer recurrence.

Table Graphic Jump LocationTable 3. Medications and Clinical Characteristics of Patients Who Underwent Endoscopic Examination During Follow-up*

The 13C-UBT was performed every year to evaluate H pylori status after successful eradication therapy (Figure 1). No newly positive 13C-UBT result was found in any of the 82 patients during the follow-up period. There was no reappearance of infection during a mean follow-up of 54 months after successful eradication of H pylori. An analysis of variance showed no statistically significant differences among the 4 treatment groups regarding the absence of H pylori reinfection.

The mean age of the 10 patients in the contrast group was 43 years (range, 17-74 years). All of them completed their scheduled follow-up visits. Recurrence of peptic ulcer and reappearance of H pylori infection were also absent in this group.

Gastrointestinal hemorrhage is the most frequent complication of peptic ulcer disease, and 20% of all patients with duodenal ulcers and 15% of all patients with gastric ulcers experience ulcer bleeding at least once in their lifetimes.10 Despite major advances in the treatment of upper gastrointestinal hemorrhage in recent years, mortality from peptic ulcer bleeding has remained significantly high2,1114 but the correct approach to prevent ulcer recurrence and further bleeding in the long term is still debated.

Before the recognition of the role of H pylori in the pathogenesis of peptic ulcer disease, maintenance therapy with H2-receptor antagonists was commonly used to prevent recurrent ulceration; high ulcer relapse rates were noted, however, ranging from 13% to 62%.15 Some studies indicated that treatment with compounds containing bismuth decreased the 1-year relapse rate compared with H2-antagonists.16,17 This may be related to suppressing effect of bismuth compounds on H pylori.18

It is now well accepted that H pylori is a major etiological factor in peptic ulcer disease.19,20 Several randomized controlled trials have shown that eradication of the organism remarkably reduces the possibility of recurrence and further bleeding in peptic ulcer disease.57,2123 The European Helicobacter pylori Study Group24 and, in the United States, the National Institutes of Health,25 advise eradication of H pylori in all cases of peptic ulcer disease, complicated or uncomplicated.

In patients with uncomplicated peptic ulcer, it is strongly recommended that H pylori eradication therapy not be followed by maintenance antiulcer treatment.24 In a long-term follow-up study, Van der Hulst et al8 found that, for up to 9.8 years after true H pylori eradication, there were no relapses of peptic ulcers in patients who had uncomplicated peptic ulcers and no maintenance therapy. However, the optimal treatment for patients with bleeding ulcers remains to be established. Limited research data are available for evaluating the long-term outcome of patients with bleeding ulcers after successful H pylori eradication (Table 4).23,26,27 No study has investigated the role of maintenance antiulcer treatment in the long-term management of patients with complicated ulcer after a successful H pylori eradication therapy. This study evaluated 3 different maintenance treatments in patients with bleeding peptic ulcers after successful eradication therapy and ulcer healing. The relapse rates of peptic ulcers and the reinfection rates of H pylori were compared among these 3 maintenance treatment groups. There were no recurrences of peptic ulcers during a mean follow-up of 56 months among the patients who received maintenance therapy after successful H pylori eradication and ulcer healing, and H pylori infection did not recur among them. However, there were also no recurrences of peptic ulcers or reinfection by H pylori among the patients who received placebo or among the patients who did not receive any maintenance treatment during the same mean follow-up of 56 months. Our results demonstrate that for patients with bleeding peptic ulcer who do not use NSAIDs, antiulcer maintenance treatment is not necessary after successful H pylori eradication and ulcer healing. Helicobacter pylori seems to be the major factor in the recurrence of peptic ulcers. Successful eradication of H pylori drastically changes the natural history of bleeding peptic ulcers.

Table Graphic Jump LocationTable 4. Peptic Ulcer Reappearance and Bleeding Recurrence After Helicobacter pylori Eradication

Proton pump inhibitor–based or ranitidine bismuth citrate–based triple therapy with clarithromycin plus amoxycillin or metronidazole for 1 week is the standard treatment for H pylori eradication. In our previous study, we found that the standard 1-week PPI-based triple therapy is effective to eradicate H pylori infection in patients with bleeding peptic ulcers.28 However, no study has reported the long-term efficacy of the 1-week PPI-based triple therapy for the eradication of H pylori in patients with complicated peptic ulcers. In this study, a newly positive 13C-UBT result was not found in any of the patients during follow-up. Reappearance of H pylori infection was not documented for up to 66 months. These findings highlight the efficacy of the 1-week PPI-based triple therapy in providing long-term H pylori eradication in patients with bleeding peptic ulcers. The reappearance of H pylori infection could be completely prevented in patients with complicated ulcers after a successful eradication therapy, even in a country with a high prevalence rate (the overall seropositive rate was 54.4% in Taiwan).29

In conclusion, the results of 5 years of follow-up observation in this randomized controlled study have shown that in patients with bleeding peptic ulcers who do not use NSAIDs, antiulcer maintenance treatment is not necessary if H pylori has been successfully eradicated and the ulcer has healed. Successful H pylori eradication therapy can change the natural course of peptic ulcers and completely prevent ulcer recurrence in patients with or without peptic ulcer complications. Finally, the 1-week PPI-based triple therapy has the efficacy to provide long-term eradication of H pylori in patients with bleeding peptic ulcers, even in a region of high prevalence.

Corresponding author and reprints: Chia-Long Lee, MD, Division of Gastroenterology, Department of Internal Medicine, Cathay General Hospital, 280, Jen-Ai Road, Section 4, Taipei 106, Taiwan (e-mail: cghleecl@hotmail.com).

Accepted for publication November 21, 2002.

This study was presented in poster form at the 12th International Workshop on Gastroduodenal Pathology and Helicobacter pylori of the European Helicobacter pylori Study Group; September 2-4, 1999; Helsinki, Finland.

This study was published in abstract form in Gut. 1999;45(suppl 3):A116.

Laine  LPeterson  WL Bleeding peptic ulcer. N Engl J Med. 1994;331717- 727
PubMed Link to Article
Vreeburg  EMSnel  Pde Bruijne  JWBartelsman  JFRauws  EATytgat  GNJ Acute upper gastrointestinal bleeding in the Amsterdam area: incidence, diagnosis, and clinical outcome. Am J Gastroenterol. 1997;92236- 243
PubMed
Rockall  TALogan  RFDevlin  HBNorthfield  TC Risk assessment after acute upper gastrointestinal hemorrhage. Gut. 1996;38316- 321
PubMed Link to Article
Brullet  ECampo  RCalvet  XCoroleu  DRivero  ESimo  DJ Factors related to the failure of endoscopic injection therapy for bleeding gastric ulcer. Gut. 1996;39155- 158
PubMed Link to Article
Tomita  TFukuda  YTamura  K  et al.  Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease. Aliment Pharmacol Ther. 2002;16 (suppl 2) 204- 209
PubMed Link to Article
Laine  LHopkins  RJGirardi  LS Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? a meta-analysis of rigorously designed trials. Am J Gastroenterol. 1998;931409- 1415
PubMed
Hopkins  RJGirardi  LSTurney  EA Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology. 1996;1101244- 1252
PubMed Link to Article
Van der Hulst  RWRauws  EAKoycu  B  et al.  Prevention of ulcer recurrence after eradication of Helicobacter pylori: a prospective long-term follow-up study. Gastroenterology. 1997;1131082- 1086
PubMed Link to Article
Dronfield  MW Upper gastrointestinal bleeding. Misiewicz  JJPounder  REVenables  CWeds.Diseases of the Gut and Pancreas 2nd ed. London, England Blackwell1994;367- 380
Riemann  JFSchilling  DSchauwecker  P  et al.  Cure with omeprazole plus amoxicillin versus long-term ranitidine therapy in Helicobacter pylori-associated peptic ulcer bleeding. Gastrointest Endosc. 1997;46299- 304
PubMed Link to Article
Rockall  TALogan  RFDevlin  HBNorthfield  TCfor the Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage, Incidence of and mortality from acute gastrointestinal haemorrhage in the United Kingdom. BMJ. 1995;311222- 226
PubMed Link to Article
Jensen  DM Heat probe for haemostasis of bleeding peptic ulcers: techniques and results of a randomized controlled trial. Gastrointest Endosc. 1990;36 (suppl) S42- S49
PubMed
Matthewson  KSwain  CPBland  MKirkham  JSBown  SGNorthfield  TC Randomized comparison of ND: YAG laser, heat probe, and no endoscopic therapy for bleeding peptic ulcer. Gastroenterology. 1990;981239- 1244
PubMed
Laine  L Multipolar peptic ulcers: electrocoagulation in the treatment of active upper gastrointestinal haemorrhage: a prospective controlled trial. N Engl J Med. 1987;3161613- 1617
PubMed Link to Article
Fisher  LRobraek-Madsen  MThomson  HHost  VWara  P Peptic ulcer hemorrhage: factors predisposing to recurrence. Scand J Gastroenterol. 1994;29414- 418
PubMed Link to Article
Miller  JPFaragher  EB Relapse of duodenal ulcer: does it matter which drug is used in initial treatment? Br Med J (Clin Res Ed). 1986;2931117- 1118
PubMed Link to Article
Martin  DFHollanders  DMay  SI  et al.  Difference in relapse rates of duodenal ulcer after healing with cimetidine or tripotassium dicitrato bismuthate. Lancet. 1981;17- 10
PubMed Link to Article
McNulty  CADent  JWise  R Susceptibility of clinical isolates of Campylobacter pyloridis to 11 antimicrobial agents. Antimicrob Agents Chemother. 1985;28837- 838
PubMed Link to Article
Howden  CW Clinical expression of Helicobacter pylori infection. Am J Med. 1996;100 (suppl 1) 27S- 34S
PubMed Link to Article
Peura  DA The report of the Digestive Health Initiative International Update Conference on Helicobacter pylori. Gastroenterology. 1997;113 (suppl 1) S4- S8
PubMed Link to Article
Graham  DYHepps  KSRamirez  FCLew  GMSaeed  ZA Treatment of Helicobacter pylori reduces the rates of rebleeding in peptic ulcer disease. Scand J Gastroenterol. 1993;28939- 942
PubMed Link to Article
Rokkas  TKarameris  AMavrogeorgis  ARallis  EGiannikos  N Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc. 1995;411- 4
PubMed Link to Article
Macri  GMilani  SSurrenti  EPassaleva  MTSalvadori  GSurrenti  C Eradication of Helicobacter pylori reduces the rate of duodenal ulcer rebleeding: a long-tem follow-up study. Am J Gastroenterol. 1998;93925- 927
PubMed Link to Article
Malfertheiner  PMegraud  FO'Morain  C  et al.  Current concepts in the management of Helicobacter pylori infection: the Maastricht 2000 Consensus report. Aliment Pharmacol Ther. 2002;16167- 180
PubMed Link to Article
National Institutes of Health Consensus Development Conference, Helicobacter pylori in peptic ulcer disease. JAMA. 1994;27265- 69
PubMed Link to Article
Lai  KCHui  WMWong  WM  et al.  Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage: a long-term randomized, controlled study. Am J Gastroenterol. 2000;952225- 2232
PubMed
Labenz  JBorsch  G Role of Helicobacter pylori eradication in the prevention of peptic ulcer bleeding relapse. Digestion. 1994;5519- 23
PubMed Link to Article
Lee  CLTu  TCWu  CH  et al.  One-week low-dose triple therapy is effective in treating Helicobacter pylori-infected patients with bleeding peptic ulcers. J Formos Med Assoc. 1998;97733- 737
PubMed
Teh  BHLin  JTPan  WH  et al.  Seroprevalence and associated risk factors of Helicobacter pylori infection in Taiwan. Anticancer Res. 1994;141389- 1392
PubMed

Figures

Place holder to copy figure label and caption

Summary of the study design and flow diagram of the progress of participants. PPI indicates proton pump inhibitor; 13C-UBT, urea breath test labeled with 100 mg of carbon 13.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. General Characteristics of 99 Patients With Bleeding Peptic Ulcers
Table Graphic Jump LocationTable 2. Medications and Clinical Characteristics of Patients Who Completed the Study*
Table Graphic Jump LocationTable 3. Medications and Clinical Characteristics of Patients Who Underwent Endoscopic Examination During Follow-up*
Table Graphic Jump LocationTable 4. Peptic Ulcer Reappearance and Bleeding Recurrence After Helicobacter pylori Eradication

References

Laine  LPeterson  WL Bleeding peptic ulcer. N Engl J Med. 1994;331717- 727
PubMed Link to Article
Vreeburg  EMSnel  Pde Bruijne  JWBartelsman  JFRauws  EATytgat  GNJ Acute upper gastrointestinal bleeding in the Amsterdam area: incidence, diagnosis, and clinical outcome. Am J Gastroenterol. 1997;92236- 243
PubMed
Rockall  TALogan  RFDevlin  HBNorthfield  TC Risk assessment after acute upper gastrointestinal hemorrhage. Gut. 1996;38316- 321
PubMed Link to Article
Brullet  ECampo  RCalvet  XCoroleu  DRivero  ESimo  DJ Factors related to the failure of endoscopic injection therapy for bleeding gastric ulcer. Gut. 1996;39155- 158
PubMed Link to Article
Tomita  TFukuda  YTamura  K  et al.  Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease. Aliment Pharmacol Ther. 2002;16 (suppl 2) 204- 209
PubMed Link to Article
Laine  LHopkins  RJGirardi  LS Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? a meta-analysis of rigorously designed trials. Am J Gastroenterol. 1998;931409- 1415
PubMed
Hopkins  RJGirardi  LSTurney  EA Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology. 1996;1101244- 1252
PubMed Link to Article
Van der Hulst  RWRauws  EAKoycu  B  et al.  Prevention of ulcer recurrence after eradication of Helicobacter pylori: a prospective long-term follow-up study. Gastroenterology. 1997;1131082- 1086
PubMed Link to Article
Dronfield  MW Upper gastrointestinal bleeding. Misiewicz  JJPounder  REVenables  CWeds.Diseases of the Gut and Pancreas 2nd ed. London, England Blackwell1994;367- 380
Riemann  JFSchilling  DSchauwecker  P  et al.  Cure with omeprazole plus amoxicillin versus long-term ranitidine therapy in Helicobacter pylori-associated peptic ulcer bleeding. Gastrointest Endosc. 1997;46299- 304
PubMed Link to Article
Rockall  TALogan  RFDevlin  HBNorthfield  TCfor the Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage, Incidence of and mortality from acute gastrointestinal haemorrhage in the United Kingdom. BMJ. 1995;311222- 226
PubMed Link to Article
Jensen  DM Heat probe for haemostasis of bleeding peptic ulcers: techniques and results of a randomized controlled trial. Gastrointest Endosc. 1990;36 (suppl) S42- S49
PubMed
Matthewson  KSwain  CPBland  MKirkham  JSBown  SGNorthfield  TC Randomized comparison of ND: YAG laser, heat probe, and no endoscopic therapy for bleeding peptic ulcer. Gastroenterology. 1990;981239- 1244
PubMed
Laine  L Multipolar peptic ulcers: electrocoagulation in the treatment of active upper gastrointestinal haemorrhage: a prospective controlled trial. N Engl J Med. 1987;3161613- 1617
PubMed Link to Article
Fisher  LRobraek-Madsen  MThomson  HHost  VWara  P Peptic ulcer hemorrhage: factors predisposing to recurrence. Scand J Gastroenterol. 1994;29414- 418
PubMed Link to Article
Miller  JPFaragher  EB Relapse of duodenal ulcer: does it matter which drug is used in initial treatment? Br Med J (Clin Res Ed). 1986;2931117- 1118
PubMed Link to Article
Martin  DFHollanders  DMay  SI  et al.  Difference in relapse rates of duodenal ulcer after healing with cimetidine or tripotassium dicitrato bismuthate. Lancet. 1981;17- 10
PubMed Link to Article
McNulty  CADent  JWise  R Susceptibility of clinical isolates of Campylobacter pyloridis to 11 antimicrobial agents. Antimicrob Agents Chemother. 1985;28837- 838
PubMed Link to Article
Howden  CW Clinical expression of Helicobacter pylori infection. Am J Med. 1996;100 (suppl 1) 27S- 34S
PubMed Link to Article
Peura  DA The report of the Digestive Health Initiative International Update Conference on Helicobacter pylori. Gastroenterology. 1997;113 (suppl 1) S4- S8
PubMed Link to Article
Graham  DYHepps  KSRamirez  FCLew  GMSaeed  ZA Treatment of Helicobacter pylori reduces the rates of rebleeding in peptic ulcer disease. Scand J Gastroenterol. 1993;28939- 942
PubMed Link to Article
Rokkas  TKarameris  AMavrogeorgis  ARallis  EGiannikos  N Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc. 1995;411- 4
PubMed Link to Article
Macri  GMilani  SSurrenti  EPassaleva  MTSalvadori  GSurrenti  C Eradication of Helicobacter pylori reduces the rate of duodenal ulcer rebleeding: a long-tem follow-up study. Am J Gastroenterol. 1998;93925- 927
PubMed Link to Article
Malfertheiner  PMegraud  FO'Morain  C  et al.  Current concepts in the management of Helicobacter pylori infection: the Maastricht 2000 Consensus report. Aliment Pharmacol Ther. 2002;16167- 180
PubMed Link to Article
National Institutes of Health Consensus Development Conference, Helicobacter pylori in peptic ulcer disease. JAMA. 1994;27265- 69
PubMed Link to Article
Lai  KCHui  WMWong  WM  et al.  Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage: a long-term randomized, controlled study. Am J Gastroenterol. 2000;952225- 2232
PubMed
Labenz  JBorsch  G Role of Helicobacter pylori eradication in the prevention of peptic ulcer bleeding relapse. Digestion. 1994;5519- 23
PubMed Link to Article
Lee  CLTu  TCWu  CH  et al.  One-week low-dose triple therapy is effective in treating Helicobacter pylori-infected patients with bleeding peptic ulcers. J Formos Med Assoc. 1998;97733- 737
PubMed
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